Accuracy of telomerase in cervical lesions: a systematic review.
ABSTRACT The detection of telomerase activity in cervix may provide information on cervical carcinogenesis and may be a marker to monitor cervical intraepithelial neoplasia transition. A quantitative systematic review was performed to estimate the accuracy of telomerase assay in cervical lesions. Studies that evaluated the telomerase test (telomerase repeated amplification protocol) for the diagnosis of cervix lesions and compared it to paraffin-embedded sections as the diagnostic standard were included. Ten studies were analyzed, which included 1069 women. The diagnostic odds ratio (DOR) for a positive telomerase test for low-grade squamous intraepithelial lesions (Lo-SIL) vs normal or benign lesions was 3.2 (95% CI, 1.9-5.6). The DOR for a positive telomerase test for high-grade squamous intraepithelial lesions (Hi-SIL) vs Lo-SIL, normal or benign lesions was 5.8 (95% CI, 3.1-10). For cervix cancer vs Hi-SIL, the DOR for a positive telomerase test was 8.1 (95% CI, 3.2-20.3) and for cervix cancer vs Lo-SIL, normal or benign lesions, it was 40.9 (95% CI, 18.2-91). Our data support the current hypothesis that telomerase may activate an early event in cervical carcinogenesis that could be associated with the initiation and progression of cervical lesions.
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ABSTRACT: The purpose of this study was to define a correlation between telomerase activity and human papillomavirus (HPV) in normal control tissue and in benign, premalignant and malignant cervical lesions. Telomerase activity was detectable in 33 out of 34 cases of squamous-cell carcinoma, five out of six cases of microinvasive carcinoma, 8 out of 20 cases and two out of six cases of high- and low-grade squamous intraepithelial lesions (SILs) respectively. The higher frequency of positive telomerase in invasive carcinoma compared with SILs was observed in both HPV-associated and non-associated groups. Whereas 92.6% of HPV-positive and 100% of HPV-negative invasive lesions expressed telomerase, only 50% of HPV-positive and 25% of HPV-negative SILs did. Interestingly, telomerase activity was also detectable in 13 out of 28 cases of benign lesions regardless of the presence of HPV. In conclusion, there may be two roles of telomerase in the cervix. The first one would present in benign lesions; the second is associated with cancer development and activated during the late stage of multistep carcinogenesis in both HPV-positive and -negative groups.British Journal of Cancer 11/1998; 78(7):933-9. · 5.08 Impact Factor
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ABSTRACT: SILs (squamous intraepithelial lesions) comprise a wide spectrum of clinically and biologically heterogeneous lesions ranging from benign proliferations to precancerous lesions. Telomerase activation plays a critical role in cellular immortalization and might be important for malignant progression. The viral oncogenes E6 and E7 are the principal transforming genes of high-risk HPVs and are important in HPV-associated immortalization and neoplastic transformation. In this study we investigated the relationship between telomerase activity, telomerase RNA, and HPV 16/18 oncogene expression in low- and high-grade SILs and SCCs (squamous cell carcinomas) of the cervix uteri. Telomerase activity was examined by the TRAP-assay and expression of the telomerase RNA (hTR) and HPV 16/18 E6/E7 oncogenes by RNA/RNA-in situ hybridization (ISH). The associated HPV-type was determined by PCR. Telomerase activity was observed in 25/29 (86%) SCCs, 31/41 (76%) high-grade SILs, 6/14 (43%) low-grade SILs, and 1/28 (3.6%) normal cervical tissues. Expression of hTR and viral oncogenes increased significantly with histopathologic severity of the lesion (p < 0.0001). A correlation was found between telomerase activity and intensity of viral oncogene expression. These findings suggest that telomerase activation occurs early in cervical carcinogenesis and is predominantly found in high-grade SILs and cervical SCCs. Our findings support current experimental data that suggest that telomerase is at least partially activated by viral oncogenes of high-risk HPV types. Telomerase activity with concomitant strong viral oncogene expression might therefore characterize a subset of lesions that are at risk for malignant progression.International Journal of Gynecological Pathology 04/2001; 20(2):177-85. · 1.41 Impact Factor
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ABSTRACT: Neoadjuvant and adjuvant chemotherapies are used adjunctively with surgery or radiation and are among the treatment options that are now employed for reducing treatment failure in early-stage cervical cancers with high-risk prognostic factors. Adjuvant therapies have been reported to significantly improve survival than would otherwise be possible with surgery or radiotherapy alone. However, for advanced cervical cancers, sequential or concurrent chemo-radiotherapy does not appear to significantly increase survival. The combination of radiotherapy with IFN-a2a and RA in the treatment of patients with locally advanced cervical cancer showed high response rates, however this should be confirmed in larger studies. Recent reports show that postoperative adjuvant radiotherapy has no benefit in survival, but that postoperative adjuvant chemotherapy has improved survival. Toxicities and the optimum number of cycles of neoadjuvant and adjuvant chemotherapy, as well as biologic therapy, will follow along with individualized treatment based on high-risk prognostic factors. Although more comprehensive studies and longer follow up will be required for complete evaluation of these adjuvant therapies, preliminary results are promising.Yonsei Medical Journal 11/1997; 38(5):255-60. · 1.31 Impact Factor